Lyme disease (LD), caused by Borrelia burgdorferi, is the most commonly reported tick-borne disease in the United States and Europe. Recent studies suggest that 300,000 cases of LD may occur in the United States each year. Antibody-based diagnostics for LD are widely utilized in clinical practice, and the Centers for Disease Control and Prevention (CDC) recommends a 2-tier approach for serologic testing. The detection of antibodies to B. burgdorferi is highly specific and sensitive in patients with late manifestations of LD; however, the sensitivity in patients with early LD is unsatisfactory (29%-40%). Direct diagnostic testing using culture or nucleic acid amplification on peripheral blood samples also has low sensitivity (≤50%) for early LD. Thus, the diagnosis of early LD is usually based on recognition of the most common clinical manifestation, an erythema migrans (EM) skin lesion. Other skin lesions, however, such as tick-bite hypersensitivity reactions, STARI (southern tick associated rash illness), and certain cutaneous fungal infections, can be confused with EM.
Given the limitations of existing diagnostics for early LD, there is a need for novel approaches that directly detect infecting spirochetes or the host's response to the pathogen.